Powder inhaler with breath flow regulation valve

ABSTRACT

There is provided a device for the administration of an inhalation medicament, including a body defining a through-going air pathway having a longitudinal axis, an air inlet, an air outlet forming a mouthpiece, means for dispensing medicament into the pathway and air flow regulating means, characterized in that the air flow regulating means includes a movable obstructing means adapted to reduce the cross-sectional area of the pathway at a location between the air inlet and the means for dispensing medicament, and biassing means, whereby the obstructing means is biassed into a first resting position in which the cross-sectional area of the pathway is minimum and is adapted to move against the bias of the biassing means to a second position in which the cross-section area of the pathway is maximum in response to a pressure fall at the mouthpiece caused by inhalation and is adapted to move farther to a third position in which the cross-sectional area of the pathway is less than maximum in response to a greater pressure fall at the mouthpiece caused by inhalation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of application Ser. No. 08/596,311,filed Jul. 17, 1996, now U.S. Pat. No. 5,727,546, which is acontinuation of PCT/GB94/01812 filed Aug. 18, 1994.

FIELD OF THE INVENTION

This invention relates to an inhalation device incorporating novel meansfor regulating the rate of patient inspiration.

BACKGROUND OF THE INVENTION

Known inhalation devices suitable for the administration to the lung ofany inhalation medicament include devices which administer themedicament in liquid form, in dry powder form or as a suspension of thesolid medicament in a liquified propellant.

Devices of the first mentioned type include nebuliser devices wherein afine respirable mist is formed by action of a compressed gas an asample, by vibration of a piezoelectric crystal or by other ultrasonicmeans; also, devices of the type described in e.g. International PatentApplication WO 91/14468, where the liquid is sprayed through a smallaperture.

Devices of the second mentioned type which may provide the medicament inunit dose or multidose form include the well known SPINHALER (RegisteredTrademark), which is described in UK Patent 1122284, the TURBUHALERRegistered Trademark) which is described in U.S. Pat. No. 4,524,769, andthe device described in European Patent Application 407028.

Devices of the third mentioned type, which generally contain apressurised reservoir of liquified propellant containing a suspension ofthe solid medicament and a metering valve for dispensing a suitabledose, are also very well known in the art and is not necessary todescribe any particular type here.

However, it is a general problem with the above devices that theefficiency of administration of an accurate dose of medicament to thelung is severely impaired in the absence of any control of the flow ofair through the device. In general, excessive inhalation velocity causesa significant proportion of the dose to impinge on the back of thethroat, with a resultant short dose reaching the target area in thelungs. This is known to be a particular problem of devices of the drypowder type which are gaining popularity due to their environmentallyfriendly attributes.

One way of alleviating this problem in a dry powder device is describedin U.S. Pat. No. 5,161,524 (Glaxo) wherein the inhalation device isprovided with a secondary air conduit as well as the primary air conduitwhich provides the path for the inhalation medicament to the lung. Ifthe air flow velocity become too great through the primary air conduit,then the secondary air conduit opens further thus decreasing the airvelocity in the primary air conduit.

However, this arrangement suffers from the disadvantage that whilst thevelocity of air in the primary conduit may be reduced, a large volume ofnon drug-containing air is drawn in through the secondary air conduit,with the result that the breath of air necessary to secure a proper dosecan become very long and drawn out. Furthermore, the arrangement may notbe suitable for all the types of inhalation device described above.

BRIEF SUMMARY OF THE INVENTION

We have now invented an inhalation device with breath rate control whichovercomes or significantly mitigates these difficulties.

There is provided a device for the administration of an inhalationmedicament, including a body defining a through-going air pathway havinga longitudinal axis, an air inlet, an air outlet forming a mouthpiece,means for dispensing medicament into the pathway and air flow regulatingmeans, characterized in that the air flow regulating means includes amovable obstructing means adapted to reduce the cross-sectional area ofthe pathway at a location between the air inlet and the means fordispensing medicament, and biasing means, whereby the obstructing meansis biased into a first resting position in which the cross-sectionalarea of the pathway is minimum and is adapted to move against the biasof the biasing means to a second position in which the cross-sectionarea of the pathway is maximum in response to a pressure fall at themouthpiece caused by inhalation and is adapted to move further to athird position in which the cross-sectional area of the pathway is lessthan maximum in response to a greater pressure fall at the mouthpiececaused by inhalation.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Thus, according to a first aspect of the invention we provide a devicefor the administration of an inhalation medicament, including a bodydefining a through-going air pathway having a longitudinal axis, an airinlet, an air outlet forming a mouthpiece, means for dispensingmedicament into the pathway and air flow regulating means, characterisedin that the air flow regulating means includes movable obstructing meansadapted to reduce the cross-sectional area of the pathway at a locationbetween the air inlet and the means for dispensing medicament, andbiassing means, whereby the obstructing means is biassed into a firstresting position in which the cross-sectional area of the pathway ismaximum and is adapted to move against the bias of the biassing means toa second position in which the cross-sectional area of the pathway isless than maximum in response to a pressure fall at the mouthpiececaused by inhalation.

By "obstructing means" we mean any element made of a material which iswholly or partially impervious to air and which is suitable forrestricting the flow of air through the pathway. The obstructing meansmay be manufactured from a metal, plastic, rubber or other suitablydense material and may be of entirely solid contruction, or it may bemade partially permeable to air by the provision of channels.

By "biassing means" we mean any means for providing a restraint tomovement against the bias on the application of pressure or suctionwhich also provides a restoring force in the opposite direction) ontithe release of pressure or suction. Suitable biassing means includesprings, where the spring may be compressed or stretched, for example,coil, torsion or leaf springs; elastomeric materials which arereversibly deformable; and resilient curved materials (including thosemade of metal, rubber or plastic) where the curve may be reversiblystraightened.

The pressure fall at the mouthpiece may desirably be amplified byproviding an air inlet which is constricted. Thus, we prefer that thecross-sectional area of the air inlet is less than the maximumcross-sectional area of the pathway. We particularly prefer that the airinlet comprises one or more apertures that have a total cross-sectionalarea of less than 25%, especially 10%, more especially 5% of the maximumcross-sectional area of the pathway.

Without prejudice to the generality of the concept, the followingcombinations of integers are preferred:

(a) the obstructing means comprises one or more partitions adapted toslide across the pathway along an axis perpendicular to the longitudinalaxis of the pathway thereby obstructing the pathway. We prefer in thiscase that the biassing means comprises a spring; or

(b) the obstructing means comprises an annular segment of membrane whichconnects two portions of the body. We particularly prefer that theobstructing means comprises a segment of membrane made of elastomericmaterial and the biassing means comprises the resistance of theelastomeric material to stretching in a direction perpendicular to thelongitudinal axis of the pathway or that that the obstructing meanscomprises an annular segment of membrane made of inelastic material andthe biassing means provides a bias against movement of the two portionsof the body towards each other along the longitudinal axis of thepathway. In this latter case, we prefer that the biassing meanscomprises a spring; or

(c) the obstructing means comprises a rigid grille or perforated sheetformed in a plane perpendicular to the longitudinal axis of the pathwayon the air inlet side of which rests a flap which in its restingposition is deflected towards the air inlet and in its second positionis urged against the grille or perforated sheet. We particularly preferthat the flap is rigid and is hinged about an axis perpendicular to thelongitudinal axis of the pathway and the biassing means comprises aspring at the hinge of the flap; or that the flap is made of a resilientelastomeric material and the biassing means consists of curvatureintroduced into the flap, said curvature being directed towards the airinlet; or

(d) the obstructing and biassing means together comprise two or morecooperating flaps made of resilient elastomeric material which in thefirst position are deflected towards the air inlet and which in thesecond position are urged together thus reducing the cross-sectionalarea of the pathway.

The air flow regulating means described above are adapted to regulatethe maximum velocity of airflow through the device. However, it isfrequently desirable to provide means not only for regulating themaximum velocity of air flow but also to regulate minimum air flow aswell.

Thus, according to a second aspect of the invention, there is provided adevice for the administration of an inhalation medicament, according tothe invention, wherein the air flow regulating means further includessecond movable obstructing means adapted to reduce the cross-sectionalarea of the pathway at a location between the air inlet and the meansfor dispensing medicament, and second biassing means, whereby the secondobstructing means is biassed into a first resting position in which thecross-sectional area of the pathway is minimum and is adapted to moveagainst the bias of the biassing means to a second position in which thecross-sectional area of the pathway is more than minimum in response toa pressure fall at the mouthpiece caused by inhalation.

We prefer that the second movable obstructing means is adapted to reducethe cross-sectional area of the pathway at a location between the firstobstructing means and the means for dispensing medicament.

We prefer that the second biassing means comprises a spring biassedalong the longitudinal axis of the device and the second obstructingmeans comprises a shutter mounted on the spring.

We prefer that the first obstructing means and biassing means comprisethe elements described above as (a) to (d). We particularly prefer thatthe first obstructing means has the construction described in (c) above.

We prefer that the cross-sectional area of the pathway when the secondobstructing means is in the first position is substantially zero.

As an alternative and preferred construction, which has the benefit ofan economy of space, the first and second obstructing means may becombined into a single element which may move between 3 positions.

Thus, according to a third aspect of the invention, we provide a devicefor the administration of an inhalation medicament, including a bodydefining a through-going air pathway having a longitudinal axis, an airinlet, an air outlet forming a mouthpiece, means for dispensingmedicament into the pathway and air flow regulating means, characterisedin that the air flow regulating means includes a movable obstructingmeans adapted to reduce the cross-sectional area of the pathway at alocation between the air inlet and the means for dispensing medicament,and biassing means, whereby the obstructing means is biassed into afirst resting position in which the cross-sectional area of the pathwayis minimum and is adapted to move against the bias of the biassing meansto a second position in which the cross-sectional area of the pathway ismaximum in response to a pressure fall at the mouthpiece caused byinhalation and is adapted to move further to a third position in whichthe cross-sectional area of the pathway is less than maximum in responseto a greater pressure fall at the mouthpiece caused by inhalation.

The following combination of integers are preferred:

(A) the obstructing means is provided with an outer groove which isretained in the housing by means of a flange within the housing aroundwhich it fits loosely; or

(B) the obstructing means is provided with an outer flange and which isretained in the housing by means of a groove within the housing withinwhich it fits loosely; or

(C) the obstructing means comprises a V-shaped vane, biassed at a hingeformed at the apex of the V, which rotates about an axis perpendicularto that of the pathway; or

(D) the pathway is divided by a partition provided with a first apertureand the obstructing means comprises a shutter provided with a secondaperture slidably engaged with the partition, which shutter is made toslide against the partition against the bias of the biassing means by apiston in gaseous communication with the mouthpiece.

In the case of (A) to (D) above, we prefer that the biassing meanscomprises a spring.

In the case of (C) above, we prefer that the biassing means comprises aspring at the hinge.

The following combination of integers is also preferred:

(E) the biassing means and obstructing means together comprise aperforated diaphragm made of resilient elastomeric material formed in aplane perpendicular to the longitudinal axis of the pathway. Weparticularly prefer that the diaphragm is provided with one or moreprotrusions on its upper and lower surfaces and is located between twopartitions formed in a plane perpendicular to the longitudinal axis ofthe pathway, the partitions being provided with apertures with whichsome or all of said protrusions cooperate to restrict or prevent thepassage of air through the apertures. We prefer the protrusion(s) to beof conical shape or to be of a shape consisting of a cone mounted on acylinder. We prefer the aperture(s) with which the protrusion(s)cooperate to be circular. We prefer that the upper and lower surfaces ofthe diaphragm are each provided with a single protrusion.

In the case of (A), (B) and (E) above, we prefer that the obstructingmeans is of substantially circular section along an axis perpendicularto the longitudinal axis of the pathway. In the case of (C) and (D)above, we prefer that the obstructing means is of substantially squareor rectangular section along an axis perpendicular to the longitudinalaxis of the pathway.

We prefer that the cross-sectional area of the pathway when theobstructing means is in the first position, is substantially zero.

The device body defining the through going-pathway will be made of arigid material, for example plastic or metal, and is preferably ofsubstantially circular or square cross-section, although the shape ofthe section may at least in part be determined by the nature of theobstructing means.

The inhalation device according to the invention is particularlysuitable for desired air flows in the range 20-250 l/min, especially30-120 l/min, particularly 40-80 l/min. Pressure reduction that may becreated between the air inlet and the mouthpiece in a device accordingto the invention, will typically be in the range 0.1-20 mbar.

It will be apparent that the air flow regulating means may be providedas an integral part of the housing of the inhalation device or as aseparately manufactured portion of the device which may be affixed tothe remainder of the inhalation device by means of a weld, a male-femaletype connection, a screw-thread or a mechanical equivalent. Theaffixation may be permanent, or it may provide for the two portions tobe attached and detached as desired, for example, to facilitate cleaningof the device. We prefer that the air flow regulating means is adaptedto be reversibly attached to and detached from the remainder of thedevice.

As a fourth aspect of the invention, we provide an air flow regulatingmeans as described above adapted for use in conjunction with a devicefor the administration of an inhalation medicament.

Inhalation devices for use in accordance with the invention include anydevice conventionally used for dispensing powdered medicament forinhalation. Suitable devices include single dose dry powder inhalerse.g. the SPINHALER (Registered Trademark) inhaler and the DISKHALER(Registered Trademark) inhaler and multi-dose powder inhalers e.g. theTURBUHALER (Registered Trademark) inhaler and the device described inEuropean Patent Application 407028.

We prefer that the device is a device for the inhalation of a drypowdered medicament or a medicament in aqueous solution. We particularlyprefer that the device is a device for the inhalation of a dry powderedmedicament.

Devices for inhalation of a medicament according to the invention areadvantageous in that they are more effective or efficient, give agreater therapeutic benefit, are safer, are easier or cheaper tomanufacture or assemble than those of the prior art. They are alsoadvantageous in that, in use, the flow of air to the patient is moredesirably or accurately controlled, the patient is able to obtain alarger or more consistent dose of medicament or they have other moredesirable properties than known inhalation devices.

Preferred embodiments of the present invention will now be described, byway of example, with reference to the accompanying drawings in which themovement of air is shown by arrows.

FIG. 1(a), shows a longitudinal section through an illustrativeinhalation device similar to the SPINHALER (Registered Trademark)incorporating air flow regulating means, according to the third aspectof the invention, in the resting position.

In subsequent figures the details of the inhalation device are omittedfor convenience.

FIG. 1(b) shows a longitudinal section through the device of FIG. 1(a)with the air flow regulating means in the second position in which thecross-sectional area of the air pathway is maximum.

FIG. 1(c) shows a longitudinal section through the device of FIG. 1(b)with the air flow regulating means in a third position in which thecross-sectional area of the pathway is less than maximum.

FIG. 1(d) shows a cross-section along line I--I of FIG. 1(a).

FIG. 2(a) shows a longitudinal section through a device according to thethird aspect of the invention showing the air flow regulating means inthe resting position.

FIG. 2(b) shows a longitudinal section through the device of FIG. 2(a)with the air flow regulating means in a second position in which thecross-sectional area of the air pathway is maximum.

FIG. 2(c) shows a longitudinal section through the device of FIG. 2(a)with the air flow regulating means in a third position in which thecross-sectional area of the pathway is less than maximum.

FIG. 2(d) shows a plan view of the device of FIG. 2(c) with the airflowregulating means in the third position taken from the direction of arrowA and in which the cross-section is circular.

FIG. 2(e) is similar to FIG. 2(d) save that the cross-section is square.

FIG. 3(a) shows a longitudinal section through a device according to thethird aspect of the invention with the air flow regulating means in theresting position.

FIG. 3(b) shows a longitudinal section through the device of FIG. 3(a)with the air flow regulating means in a second position in which thecross-sectional area of the air pathway is maximum.

FIG. 3(c) shows a longitudinal section through the device of FIG. 3(a)with the air flow regulating means in a third position in which thecross-sectional area of the pathway is less than maximum.

FIG. 4(a) shows a longitudinal section through a device according to thethird aspect of the invention with the air flow regulating means in theresting position.

FIG. 4(b) shows a longitudinal section through the device of FIG. 4(a)with the air flow regulating means in a second position in which thecross-sectional area of the air pathway is maximum.

FIG. 4(c) shows a longitudinal section through the device of FIG. 4(a)with the air flow regulating means in a third position in which thecross-sectional area of the pathway is less than maximum.

FIG. 5(a) shows a longitudinal section through a device according to thethird aspect of the invention with the air flow regulating means in theresting position.

FIG. 5(b) shows a longitudinal section through the device of FIG. 5(a)with the air flow regulating in a second position in which thecross-sectional area of the air pathway is maximum.

FIG. 5(c) shows a longitudinal section through the device of FIG. 5(a)with the air flow regulating means in a third position in which thecross-sectional area of the pathway is less than maximum.

FIG. 6(a) shows a longitudinal section through a device according to thesecond aspect of the invention with an air flow regulating means havingfirst and second obstructing means in the resting position.

FIG. 6(b) shows a longitudinal section through the device of FIG. 6(a)wherein the second obstructing means is in a second position in whichthe cross-sectional area of the air pathway is more than minimum.

FIG. 6(c) shows a longitudinal section through the device of FIG. 6(b)wherein the first obstructing means is in a second position in which thecross-sectional area of the pathway is less than maximum.

FIG. 7(a) shows a longitudinal section through a device according to thefirst aspect of the invention with the air flow regulating means in theresting position.

FIG. 7(b) shows a longitudinal section through the device of FIG. 7(a)with the air flow regulating means in a second position in which thecross-sectional area of the pathway is minimum.

FIG. 8 shows a longitudinal section through a device according to thefirst aspect of the invention with the air flow regulating means in theresting position.

FIG. 9(a) shows a longitudinal section through a device according to thefirst aspect of the invention with the air flow regulating means in theresting position.

FIG. 9(b) shows a longitudinal section through the device of FIG. 9(a)with the air flow regulating means between the first and secondpositions.

FIG. 10(a) shows a longitudinal section through a device according tothe first aspect of the invention with the air flow regulating means inthe resting position.

FIG. 10(b) shows a longitudinal section through the device of FIG. 10(a)with the air flow regulating means between the first and secondpositions.

FIG. 11(a) shows a longitudinal section through a device according tothe first aspect of the invention with the air flow regulating means inthe resting position.

FIG. 11(b) shows a longitudinal section through the device of FIG. 11(a)with the air flow regulating means between the first and secondpositions.

FIG. 12(a) shows a longitudinal section through a device according tothe first aspect of the invention with the air flow regulating means inthe resting position.

FIG. 12(b) shows a longitudinal section through the device of FIG. 12(a)with the air flow regulating means between the first and secondpositions.

FIG. 13 shows the results of experimental tests performed on embodimentsof the invention.

Referring now to FIG. 1(a) in more detail, a dry powder inhalationdevice comprises a generally cylindrical body defining a through-goingpathway, said body comprising a mouth piece portion 1, a closure portion2 and an air-flow regulator portion 3. Closure portion 2 is provided, atits end which connects with mouthpiece portion 1, with a peripheralflange 4 within which the end of mouthpiece portion 1 fits closely. Airflow regulator portion 3 is provided, at its end which connects withclosure portion 2, with a peripheral flange 5 within which the end ofclosure portion 2 fits closely. At its end remote from air flowregulator portion 3, mouthpiece portion I is tapered to form afrustoconical mouthpiece 6. Within mouthpiece portion 1 a simple bearing7 is supported by cross members 8. A spindle 9 is seated in bearing 7.Spindle 9 is provided with a cup 10 which is capable of closelyreceiving a perforated capsule 11 containing medicament to be inhaled,which together form means for dispensing medicament. Spindle 9 is alsoprovided with rotor vanes 12 which cause spindle 9 to rotate withinbearing 7 when air is drawn through the device, as during inhalation.Closure portion 2 is provided, at its end remote from the mouthpieceportion 1, with a perforated grid 13.

Air flow regulator portion 3, having an air inlet aperture 14 in firstpartition 15 is provided with a second partition 16 on the mouthpieceside of the first partition 15 in between which two partitions islocated a perforated diaphragm 17. Perforated diaphragm 17 is providedwith a protrusion 18 on the inlet side which cooperates with and closesair inlet aperture 14 in first partition 15 in the resting position anda protrusion 19 on the outlet side which is adapted to cooperate withand close an aperture 20 in second partition 16 in response to apressure drop at the mouthpiece caused by inhalation. Second partition16 also contains further apertures 21.

Referring now to FIG. 1(b), in use, when the pressure at the mouthpiece(not shown) is reduced on inhalation, the perforated diaphragm 17 isdistorted and protrusion 18 moves away from air inlet aperture 14 infirst partition 15 thus allowing the flow of air through the pathway viaperforations in the diaphragm 17.

Referring now to FIG. 1(c), when the pressure at the mouthpiece isfurther reduced, protrusion 19 on the air outlet side of perforateddiaphragm 17 is urged against aperture 20 in second partition 16 thusreducing the cross-sectional area of the pathway and restricting theflow of air.

FIG. 1(d) shows a possible arrangement of perforations in diaphragm 17.

As variants of the embodiment shown in FIG. 1, perforated diaphragm 17may be provided with any number of protrusions 18 to its surface on theair inlet side which cooperate with an equal number of apertures 14 infirst partition 15. In an alternative arrangement, there may exist anexcess number of apertures 14 over the number of protrusions 18.Equally, perforated diaphragm 17 may be provided with one or moreprotrusions 19 to its surface on the outlet side which cooperate with anequal number of apertures 20 in second partition , or the number ofapertures 20 in partition 16 may exceed the number of protrusions 19 onperforated diaphragm 17.

In FIGS. 2 to 12 which follow, the details of construction of portions 1and 2 of the inhalation device are omitted but may readily beascertained by reference to FIG. 1(a).

Referring now to FIG. 2(a) the air flow regulator portion 3 of theinhalation device, comprises an air inlet 22 and contains a hingedV-shaped vane 27 having two portions 23 and 24 which is able to rotateabout an axis perpendicular to the pathway at a hinge 25 (shown in FIGS.2(d) and 2(e)) against the bias of spring 26. In the resting position,the cross-sectional area of the pathway is substantially zero.

Referring now to FIG. 2(b), when the pressure at the mouthpiece (notshown) is reduced on inhalation, vane 27 rotates about its axis againstthe bias of spring 26, thus increasing the cross-sectional area of thepathway and allowing the flow of air. At a point at which the vane hashalf rotated, the flow of air is maximum.

Referring now to FIG. 2(c), when the pressure at the mouthpiece isfurther reduced, the vane 27 further rotates until it is unable torotate any further at which point the flow of air is again minimised.

The two portions 23, 24 of vane 27 may be gas impermeable, in which casethe flow of air at rest and at minimum pressure at the mouthpiece willbe entirely prevented, or either or both portions may be perforated, inwhich case some flow of air will be allowed when the flow regulatorportion 3 of the inhalation device is in the first or third positions.

Referring now to FIG. 3(a), air flow regulator portion 3 of theinhalation device comprises an air inlet 22 and is provided with anannular flange 28 which retains a disc 29 having a central channel 30and an outer groove 31 in which the flange 28 fits loosely. The groove31 in disc 29 is biased against the air outlet side of flange 28 bymeans of spring 32 which is supported by a protrusion 33 on flange 28.

Referring now to FIG. 3(b), when the pressure at the mouthpiece (notshown) is reduced on inhalation, the disc 29 moves against the bias ofspring 32 thus creating a space between the flange 28 and the groove 31on the disc 29 through which air may flow.

Referring now to FIG. 3(c), when the pressure at the mouthpiece isfurther reduced, the disc 29 moves further against the bias of spring 32and the space formed between the flange 28 and the groove 31 on the disc29 is closed. Thus the cross-sectional area of the pathway is decreasedto that value in the resting position (FIG. 3(a)).

Referring now to FIG. 4(a), air flow regulator portion 3 of theinhalation device comprises an air inlet 22 and contains a partition 34provided with a first aperture 35. Aperture 35 is, in the restingposition, closed by a shutter 36 provided with a second aperture 37,which shutter is slidably engaged with the partition. Movement of theshutter 37 is controlled by a piston 38 retained in piston housing 39which forms part of the housing of flow regulator portion 3 and which isbiased against one or more springs 40. The piston 38 is in gaseouscommunication with the air outlet at the mouthpiece (not shown) by meansof a channel 41 connecting the piston housing 39 and a part of the airnow regulator portion 3 on the air outlet side of the shutter 36.

Referring now to FIG. 4(b), when the pressure at the mouthpiece (notshown) is reduced on inhalation, the piston 38 is urged against the biasof spring(s) 40, and the shutter 36 moves bringing second aperture 37into communication with first aperture 35.

Referring now to FIG. 4(c), as the pressure at the mouthpiece is furtherreduced, the piston 38 is urged further against the bias of spring(s) 40and the aperture 37 in shutter 36 moves out of communication with theaperture 35 in partition 34, thus restricting the flow of air.

The relative dimensions of apertures 35 and 37 and the distance oftravel of piston 38 may be such that the pathway is completely closed atrest when a pressure drop is produced at the mouthpiece, or that thecross-sectional area of the pathway under these conditions is small.

Referring now to FIG. 5(a), air flow regulator portion 3 of theinhalation device comprises an air inlet 22 and is provided with acircumferential groove 42 which retains a disc 43 having a centralchannel 44 and an outer flange 45 around which the groove 42 fitsloosely. The flange 45 an disc 43 is biased against the inlet side ofgroove 42 in the housing by means of spring 46 which is supported by abase 47. Base 47 is illustrated as a grille; however it mayalternatively consititute a protrusion into the pathway from the wall ofthe air flow regulator portion 3 at a point on the outlet side of thegroove 42, or a cross-piece, or it may constitute some other mechanicalequivalent which will be apparent to a person skilled in the art.

Referring now to FIG. 5(b), when the pressure at the mouthpiece (notshown) is reduced on inhalation, the disc 43 moves against the bias ofspring 46 thus creating a space between the flange 45 on the disc 43 andthe groove 42 through which air may flow.

Referring now to FIG. 5(c), when the pressure at the mouthpiece isfurther reduced, the disc 43 moves further against the bias of spring 46and the space formed between the flange 45 on the disc 43 and the groove42 is closed. Thus the cross-sectional area of the pathway is decreasedto that value in the resting position (FIG. 5(a)).

In FIGS. 3 and 5, we prefer that the air flow regulator portion 3 anddisc 29 or 45 are of circular section. However, they may also be ofanother shaped section, for example, of rectangular or square section.

Furthermore, it will be apparent to the skilled person that disc 29 or45 may have any number of channels which may be arranged as desired.Alternatively, although this is not preferred, they may be entirelysolid in which case the minimum flow rate will be zero.

Referring now to FIG. 6(a), air flow regulator portion 3 of theinhalation device, having an air inlet aperture 14 in first partition 15is provided with a second perforated partition 16 towards the outlet, inbetween which is located a shutter 48 which is urged against air inletaperture 14 by the bias of spring 49 and a curved resilient flap 50 madeof elastomeric material which rests against second partition 16 on theair inlet side of second partition 16 and in which the curvature of theflap 50 is directed towards the air inlet.

Referring now to FIG. 6(b), in use, when the pressure at the mouthpiece(not shown) is reduced on inhalation, the shutter 48 moves away from theair inlet aperture 14 in first partition 15 against the bias of spring49 thus allowing air to be drawn through the device.

Referring now to FIG. 6(c), when the pressure at the mouthpiece isfurther reduced, the flap 50 is urged against partition 16 withlessening of its curvature thereby reducing the cross-sectional area ofthe pathway and restricting the flow of air. Should the suction appliedat the mouthpiece be reduced, the curvature of the flap is restored andthe cross sectional area through which the air may pass is increased. Inthis way the flow of air through the device is regulated.

Referring now to FIGS. 7(a) and 7(b), air flow regulator portion 3 ofthe inhalation device having an air inlet 22 is provided with a grilleor perforated partition 16 on the air inlet side of which rests a curvedresilient flap 50 made of elastomeric material, the curvature of whichflap is directed towards the air inlet. The operation of the device inresponse to a varying strength suction applied at the mouthpiece isessentially as described above for FIGS. 6(b) and 6(c).

In FIG. 8, the curved resilient flap 50 of FIG. 7 is replaced by arotatable rigid flap 51 which is hinged at the wall of the housing ofthe air flow regulator portion 3 such that the axis of rotation isperpendicular to the direction of air flow. At rest, the rigid flap 51is biassed towards the air inlet by spring 52 located at the hinge. Asthe pressure at the mouthpiece (not shown) is reduced, rigid flap 51 isurged against perforated partition 16 thereby reducing thecross-sectional area of the air pathway and restricting the flow of air.

In FIG. 9(a), the housing of the air flow regulator portion 3 of theinhalation device, which we prefer to be of square section, and which isprovided with an air inlet 22, contains two cooperating flaps 53, 54 ofresilient elastomeric material which are deflected towards the airinlet.

Referring to FIG. 9(b), when the pressure at the mouthpiece (not shown)is reduced on inhalation, the flow of air through the pathway causesflaps 53 and 54 to be urged together, thus causing a reduction in thecross-sectional area of the pathway. The flow of air through the outletis thus regulated in a similar manner to the embodiments shown in FIGS.7 and 8.

Furthermore, a device similar to the embodiment shown in FIG. 9 may beimagined in which flaps 53, 54 are replaced by a larger number of flapsin a frusto-conical arrangement in which case the cross-section of theair flow regulator portion 3 is desirably circular.

Referring now to FIG. 10(a), air flow regulator portion 3 of theinhalation device, consists of two portions 55 and 56, the former ofwhich is provided with a constricted air inlet 14, the two portions ofthe housing being connected by an annular segment of membrane made ofthin elastomeric material 57 held rigid by the presence of two or moresolid supports 58.

Referring now to FIG. 10(b), as the pressure at the mouthpiece (notshown) is reduced on inhalation, a pressure difference (amplified by theconstriction at air inlet 14) is created across the membrane 57 causingit to stretch against its bias into the air pathway. The air pathway isobstructed and its cross-sectional area is in this way reduced. As thepressure drop at the mouthpiece is reduced, the membrane 57 relaxestowards its rest position and the cross-sectional area of the pathwaythrough which the air may pass is increased towards its maximum value.The stretching and relaxing of the membrane 57 is sensitive to thesuction applied at the mouthpiece, and thus the flow of air through thedevice is regulated.

As a variant of the embodiment shown in FIG. 10 we envisage a furtherembodiment in which the elastomeric membrane is present not as anannular segment, but as two part semi-annular segments locateddiametrically opposite each other and in which the supports 58 areformed as an integral part of the housing tube. This variant on thetenth embodiment can be expected to operate in the same manner as thetenth embodiment, although it may have further advantages for example inease of manufacture.

Referring now to FIG. 11(a), air flow regulator portion 3 of theinhalation device is of circular section and consists of two portions 55and 56, the former of which is provided with a constricted air inlet 14,the two portions of the housing being connected by an annular segment ofmembrane made of inelastic material 57 held rigid and extended by thepresence of spring 59.

Referring now to FIG. 11(b), as the pressure at the mouthpiece (notshown) is reduced on inhalation, a pressure difference is created acrossthe membrane 57 causing it to crumple into the pathway. As the membrane57 is inelastic, the two portions of the housing are drawn togetheragainst the bias of spring 59. The pathway is obstructed and itscross-sectional area is in this way reduced. As the pressure drop at theoutlet is reduced the spring 59 relaxes and the membrane 57 returnstowards its rest position. The cross-sectional area of the pathwaythrough which air may pass is thus increased towards its maximum value.In this way, and in a similar manner to the tenth embodiment, the flowof gas through the outlet is regulated.

As a variant of the embodiment shown in FIG. 11, we envisage a furtherembodiment in which the two portions of the air flow regulator portion 3have square section separated by a segment of membrane made of inelasticmaterial wherein this segment contains creases so that it is capable ofcompressing concertina fashion with simultaneous reduction in itscross-sectional area in the manner of an old-fashioned camera bellows.

Referring now to FIG. 12(a), air flow regulator portion 3 of theinhalation device, having constricted air inlet 14 contains along itslength two partitions 60 retained in pockets 61 in the housing of theair flow regulator portion 3, with which they form an airtight seal.Partitions 60 are adapted to slide along an axis perpendicular to thelongitudinal axis of the device, and are in gaseous communication withthe outside of the housing through airholes 62. Springs 63 biaspartitions 60 into their resting position within pockets 61.

Referring now to FIG. 12(b), as the pressure at the mouthpiece (notshown) is reduced on inhalation, a pressure difference is createdbetween the inside and outside faces of the partitions 60 causing themto slide in a direction perpendicular to the longitudinal axis of thedevice against the bias of springs 63. The pathway is obstructed and itscross-sectional area is reduced. As the pressure reduction at the outletis reduced, the springs 63 relax and the partitions 60 return to theirrest positions within pockets 61. The cross-sectional area of thepathway through which the air may pass is thus increased towards itsmaximum value. In this way, the flow of air through the device isregulated.

Although it is not preferred, it can be seen that a variant on thetwelth embodiment may be provided which comprises only a singlepartition 60, but which will nevertheless operate in a similar manner.

It may be envisaged in the embodiments shown in FIGS. 1, 5, 6, 7 and 8in order to improve compactness of the device that perforated grid 13may be omitted from the construction, particularly if the closureportion 2 and the air flow regulator portion 3 are moulded as one piecerather than two.

Embodiments were tested experimentally to investigate their air flowcharacteristics as follows:

Experimental Test 1

An inhalation device according to the invention was constructed whichcomprised a conventional SPINHALER (Registered Trademark) and an airflow regulator portion as illustrated in FIG. 6 in which the size ofaperture 14 was 6.3 mm, the inside diameter of the housing of the airflow regulator portion was 20.7 mm, the elastomeric flap 50 was circularand manufactured of vulcanised rubber and the spring 49 consisted of asingle turn of fine steel wire.

The device was tested using a vacuum generator to simulate patientinhalation. A maximum flow-rate was obtained at 41 l/min, which flowrate is known to be in the desirable range for efficient inhalation ofdry-powdered medicament.

Experimental Test 2

An air flow regulator portion for an inhalation device according to theinvention was constructed as illustrated in FIG. 1 in which the insidediameter of the air flow regulating portion 3 was 50 mm, the diameter ofthe aperture 14 was 5 mm, diaphragm 17 was constructed of siliconerubber of thickness 0.95 mm and protrusions 18 and 19 were manufacturedof a rigid plastics material (acetal). Protrusions 18 and 19 wereaffixed to the diaphragm by means of a screw fixture on protrusion 18which passed through the diaphragm 17 into a threaded socket withinprotrusion 19. An airtight cooperation between protrusion 18 andaperture 14 in the resting position was ensured by the provision of a 3mm thick foam rubber surround to aperture 14. Diaphragm 17 contained asingle circular perforation of diameter 5 mm.

Three tests were performed with other dimensions as follows:

Test 2(a)

Diameter of the aperture 20: 6 mm;

Protrusion 18 consisted of a cone of height 10 mm and conical angle 40°sitting on cylindrical base of height 3 mm;

Protrusion 19 consisted of a cone of height 4 mm and conical angle 45°sitting on a cylindrical base of height 3 mm;

Distance between partition 15 and diaphragm 17: 3 mm;

Distance between partition 16 and diaphragm 17: 13 mm.

Test 2(b)

Dimensions as with Test 2(a) except for the following:

Distance between partition 15 and diaphragm 17: 2 mm;

Distance between partition 6 and diaphragm 17: 11 mm.

Partition 15 was provided with a second aperture of diameter 5 mm.

Test 2(c)

Dimensions as with Test 2(b) except for the following:

Distance between partition 15 and diaphragm 17: 3 mm;

Distance between partition 16 and diaphragm 17: 13 mm.

The characteristics of the air flow regulator portion of the device weretested by application of a vacuum. A profile of flow rate deliveredagainst pressure drop across the portion is shown in FIG. 13.

The S-shaped profiles of tests 2(a), 2(b) and 2(c) illustrate minimumand maximum flow control characteristics of the device according to theinvention.

It is to be expected that a person skilled in the art could with routineexperimentation optimise the parameters above to obtain flows inresponse to a pressure drop within a desired range.

What is claimed is:
 1. A device for controlling the administration ofinhalation medicament comprising an air inlet, an air outlet and airflowregulating means, said means comprising a movable obstructing meansadapted to reduce the cross-sectional area of the pathway at a locationbetween the air inlet and the air outlet and biasing means, theobstructing means being biased into a first resting position in whichthe cross-sectional area of the pathway is maximum and being adapted tomove against the bias of the biasing means to a second position in whichthe cross-sectional area of the pathway is less than maximum in responseto a pressure fall at the air outlet, wherein the airflow regulatingmeans further includes second movable obstructing means adapted toreduce the cross-sectional area of the pathway at a location between theair inlet and the air outlet and second biasing means, the secondobstructing means being biased into a first resting position in whichthe cross-sectional area of the pathway is minimum and being adapted tomove against the bias of the biasing means to a second position in whichthe cross-sectional area of the pathway is more than minimum in responseto a pressure fall at the air outlet.
 2. A device for controlling theadministration of an inhalation medicament comprising an air inlet, anair outlet and airflow regulating means, wherein the airflow regulatingmeans includes movable obstructing means adapted to reduce thecross-sectional area of the pathway at a location between the air inletand the air outlet and biasing means, the obstructing means being biasedinto a first resting position in which the cross-sectional area of thepathway is minimum and being adapted to move against the bias of thebiasing means to a second position in which the cross-sectional area ofthe pathway is maximum in response to a pressure fall at the air outletand being adapted to move further to a third position in which thecross-sectional area of the pathway is less than maximum in response toa greater pressure fall at the air outlet.
 3. A device for controllingthe administration of inhalation medicament comprising an air inlet, anair outlet forming a connection to a device for administration of aninhalation medicament, and airflow regulating means, said meanscomprising a movable obstructing means adapted to reduce thecross-sectional area of the pathway at a location between the air inletand the air outlet and biasing means, the obstructing means being biasedinto a first resting position in which the cross-sectional area of thepathway is maximum and being adapted to move against the bias of thebiasing means to a second position in which the cross-sectional area ofthe pathway is less than maximum in response to a pressure fall at theair outlet, wherein the airflow regulating means further includes secondmovable obstructing means adapted to reduce the cross-sectional area ofthe pathway at a location between the air inlet and the air outlet andsecond biasing means, the second obstructing means being biased into afirst resting position in which the cross-sectional area of the pathwayis minimum and being adapted to move against the bias of the biasingmeans to a second position in which the cross-sectional area of thepathway is more than minimum in response to a pressure fall at the airoutlet.
 4. A device for controlling the administration of an inhalationmedicament comprising an air inlet, an air outlet forming a connectionto a device for administration of an inhalation medicament, and airflowregulating means, wherein the airflow regulating means includes movableobstructing means adapted to reduce the cross-sectional area of thepathway at a location between the air inlet and the air outlet andbiasing means, the obstructing means being biased into a first restingposition in which the cross-sectional area of the pathway is minimum andbeing adapted to move against the bias of the biasing means to a secondposition in which the cross-sectional area of the pathway is maximum inresponse to a pressure fall at the air outlet and being adapted to movefurther to a third position in which the cross-sectional area of thepathway is less than maximum in response to a greater pressure fall atthe air outlet.